Halohydrin thiol dienoates

ABSTRACT

ALIPHATIC 2,4-DI-UNSATURATED THIOLESTERS USEFUL AS INTERMEDIATES AND FOR THE CONTROL OF INSECTS OF THE FORMULA:   R4-C(-Z&#39;&#39;)(-R3)-CH(-Z)-(CH2)N-CH(-R2)-(CH2)M-CH=CH-C(-R1)=   CH-CO-S-R10   WHEREIN:   M IS ZERO OR THE POSITIVE INTEGER ONE, TWO OR THREE; N IS THE POSITIVE INTEGER ONE, TWO OR THREE; Z IS BROMO, CHLORO, FLUORO OR HYDROXY; Z&#39;&#39; IS BROMO, CHLORO, FLUOROR OR HYDROXY; AND R10 IS LOWER ALKYL, PROVIDED THAT WHEN Z&#39;&#39; IS BROMO, CHLORO OR FLUORO, THEN Z IS HYDROXY AND WHEN Z&#39;&#39; IS HYDROXY, THEN Z IS BROMO, CHLORO OR FLUORO R&#39;&#39;=HYDROGEN OR LOWER ALKYL AND R2, R3, R4 AND LOWER ALKYL.

United States Patent 3,781,322 HALOHYDRIN THIOL DIENOATES Clive A.Henrick, 1621 Channing Ave. 94304, and John B. Siddall, 2470 Greer St.94303, both of Palo Alto, Calif.

No Drawing. Original application Feb. 16, 1971, Ser. No. 115,725, nowPatent No. 3,706,733. Divided and this application Aug. 18, 1972, Ser.No. 281,887

Int. Cl. C07c 153/07 US. Cl. 260455 R 10 Claims ABSTRACT OF THEDISCLOSURE Aliphatic 2,4-di-unsaturated thiolesters useful asintermediates and for the control of insects of the formula:

' R R R o R -C lCH-(CHzM-H (CHz)mCH=CH( =CH Rs wherein:

m is zero or the positive integer one, two or three;

n is the positive integer one, two or three;

Z is bromo, chloro, fluoro or hydroxy;

Z is bromo, chloro, fluoro or hydroxy; and

R is lower alkyl, provided that when Z is bromo, chloro or fluoro, thenZ is hydroxy and when Z is hydroxy, then Z is bromo, chloro or fluoroR'=hydrogen or lower alkyl and R R R are lower alkyl.

This is a division of application Ser. No. 115,725, filed Feb. 16, 1971,now US. Pat. 3,706,733.

This invention relates to novel polyunsaturated aliphatic compounds,novel intermediates therefor, syntheses thereof and to the control ofarthropods. The novel polyunsaturated aliphatic compounds arerepresented by the following Formula A:

m is zero or the positive integer one, two or three;

n is the positive integer one, two or three;

Z is hydrogen, bromo, chloro, fluoro or hydroxy;

Z is bromo, chloro, fluoro, ---OR*, or, taken together with Z, oxido,epithio, imino or carbon-carbon bond;

R is hydrogen or alkyl;

each of R R and R is alkyl;

R is one of the groups CEN, -CH -X,

The compounds of Formula A are useful for the control of arthropods,particularly insects. The compounds are applied using suitable carriersubstances, such as either 3,781,322 Patented Dec. 25, 1973 ice liquidor solid carriers, such as water, acetone, cottonseed oil, xylene,mineral oil, silica, talc, natural and synthetic resins, and the like.Generally, compositions for application will contain up to about of theactive compound and more usually less than 25%, sufiicient compositionshould be applied to provide from about 0.1 to 25 micrograms of theactive compound per insect. Typical insects controlled by the presentinvention are Diptera, such as mosquitos and houseflies; Hemiptera, suchas Pyrrhocoridae and Miridae; Lepidopteran, such as Pyralidae, Noctuidaeand Gelechiidae; and Coleoptera, such as Tenebrionidae, Chrysomelidaeand Dermestidae. For example, Pyrrhocoris apterus, Lygus hesperus,Aphids, Tenebrio malitor, Triboleum confusm, Diabroticaduodecimpunctata, Dermestes maculatus, alfalfa Weevil, Potato tubermoth,Aedes aegypti and Musca domestica. Without any intention of being boundby theory, the compounds of Formula A are believed to be effective byreason of hormonal action in that unlike conventional insecticides whichare effective by reason of causing immediate death, the compounds ofFormula A are efiective by reason of physiological changes caused in thetreated insect which result in eventual death of the insect and/orinability of the treated insect to reproduce by reason of sterility orabnormal development.

In the description hereinafter, each of R through R X, Z, Z, m and n isas defined hereinabove.

The compounds of the present invention are prepared according to thefollowing outlined syntheses:

(A; R is CH20H) In the above outline process, an aldehyde of Formula Iis reacted with a carbanion of Formula IA or by Wittig reaction using anylid of Formula IE to produce a compound of Formula II (R is cycloalkylor phenyl).

A compound of Formula II is reacted with a dialkyl phosphonoacetonitrilein the presence of base, such a an alkali metal hydride or alkali metalalkoxide, in an organic solvent, such as a hydrocarbon, ether ordialkylsulfoxide, e.g. tetrahydrofuran, benzene, dimethylsulfoxide,toluene, dimethylformamide, and the like, to prepare the novel nitrilesof Formula A.

The esters of Formula III are prepared by the reaction of a compound ofFormula II with carbanion of dialkyl carbalkoxy-methylphosphonate asdescribed in our copending application Ser. No. 111,766, filed Feb. 1,1971,

now abandoned, the disclosure of which is incorporated by reference.Reduction of an ester of Formula III using lithium aluminum hydride, orthe like, affords the allylic alcohols of Formula A (R is CH OR" inwhich R is hydrogen).

Ethers of the alcohols are prepared by etherification of the alcohol ofFormula A or by first converting the alcohol into the correspondingbromide or chloride (R is CH --X) and then reacting the halide with thesalt of an alcohol according to the ether moiety desired. The halidesalso serve as precursors for the preparation of the novel thiols,thioethers and amines of the present invention. Thus, reaction of ahalide of Formula A with thiourea or hydrogen sulfide yields the novelthiols. The thioethers of the present invention are then prepared from ahalide of Formula A by reaction with a mercaptan or from the thiol. Theamines of Formula A are prepared by reaction of halide of Formula A withthe desired amine.

The thiolesters of Formula A are prepared from the acid chloride byreaction with alkylmercaptan or alkyl lead mercaptide.

The novel epoxide of Formula A (Z' taken together with Z is oxido) areprepared by reacting a tri-unsaturated compound of Formula A (2' takentogether with Z is a carbon-carbon bond) with an organic peracid, suchas perphthalic acid or perbenzoic acid, in an organic solvent. Theepoxides serve as precursors for producing the episulfides (A; Z takentogether with Z is epithio) by reaction with potassium thiocyanate orammonium thiocyanate in an organic olvent, such as a lower alcohol. Thenovel mono-halo compounds of Formula A (Z' is bromo, chloro or fluoroand Z is hydrogen) are prepared by treating a tri-unsaturated compoundof Formula A with one equivalent of dry hydrogen halide in a halogenatedhydrocarbon solvent of low dielectric constant. The dihalo compounds ofFormula A (each of Z and Z 1s bromo, chloro or fluoro) are produced bytreating a triene of Formula A with one equivalent of dry bromine,chlorine or fluorine in a halogenated hydrocarbon solvent.

The mono-hydroxy compounds of Formula A (Z' is hydroxy, Z is hydrogen)are produced by the addition of water to the terminal olefinic bondusing a mercuric salt followed by reduction of the oxy-mercurialintermediate in situ. Suitable mercuric salts include mercuric acetate,mercuric nitrate, mercuric trifiuoroacetate, mercuric acylates andmercuric halides. Suitable reducing agents include the borohydrides,hydrazine and sodium amalgam. See Brown and Rei, I. Am. Chem. Soc. 91,5646 (1969); Brown et al., I. Am. Chem. Soc. 89, 1522 and 1524 (1967);and Wakabayashi, J. Med. Chem. 12, 191 (January 1969). By conducting thereaction in the presence of an alcohol (K -OH) such as methanol,ethanol, isopropyl alcohol, benzyl alcohol, cyclopentanol, and the like,the corresponding ether is prepared. The compounds of Formula A, whereinR is carboxylic acyl, are prepared from a compound of Formula A, whereinR is hydrogen, by reaction with a carboxylic acid chloride or bromide orcarboxylic acid anhydride in pyridine or by treatment with a carboxylicacid anhydride in the presence of sodium acetate. The reaction isgenerally conducted at about room temperature to reflux temperature forabout one to forty-eight hours, shorter reaction time being favored bytemperatures above room temperature.

The novel aziridines of Formula A (Z' taken together with Z is imino)are prepared as follows:

In the above formulas X is bromo or chloro and R is methyl or tolyl.

In the practice of the above process, a haloketone of Formula IV isreacted with an alkali azide, such as sodium azide, in an organicsolvent, such as dimethylformamide, dimethylacetamide, and the like, atroom temperature or above to afiord the 11-azido compound (V). Theazidoketone (V) is then reduced using sodium borohydride or otherreducing agent to yield the corresponding lO-hydroxy-ll-azido or FormulaVI. A compound of Formula VI is treated with tosyl or mesylchloride intricthylamine, pyridine, or the like, to form the sulfone (VII). Acompound of Formula VII is then reduced using a reducing agent formed ofsodium borohydride and a transition metal, such as a lower valencecobaltous halide. The reducing agent can be formed in the presence orabsence of dipyridyl. The reduction and formation of the reducing agentcan be carried out in an organic solvent, such as ethanol, methanol,tetrahydrofuran, and other high boiling others.

The haloketones (IV) are prepared from the corresponding halohydrin (A;Z is bromo or chloro and Z is hydroxy) by oxidation using Jones reagentor chromium trioxide/pyridine. The halohydrin is prepared by treat mentof an epoxide of Formula A with HCl or HBr in the presence of waterwhich affords ll-hydroxy-lO-halo, as well, which can be separated bychromatography.

Another embodiment of the present invention is the aziridines of thealkyl ester (III) which can be prepared by the aforementioned procedure.These compounds are used for the control of insects in the same way asthe compounds of Formula A.

As alternative syntheses embraced in the outlined syntheses above, amono-unsaturated aldehyde of Formula I (Z taken together with Z is acarbon-carbon bond) can first be elaborated using the methods describedabove and thereafter converted into the carbonyl of Formula II which isthen converted into the compounds of Formula A.

The term alkyl, as used herein, refers to a straight or branched chainsaturated aliphatic hydrocarbon group having a chain length of one totwelve carbon atoms, such as methyl, ethyl, n-propyl, i-propyl, n-butyl,n-hexyl, namyl, n-heptyl, n-octyl, n-nonyl, lauryl, n-decyl, t-amyl,3-ethylpentyl and 2-methylhexyl. The term hydroxyalkyl, as used herein,refers to an alkyl group substituted with one hydroxy group, e.g.hydroxymethyl, p-hydroxyethyl and 4-hydroxypentyl. The term alkoxyalkyl,as used herein, refers to an alkyl group substituted with one alkoxygroup, e.g. methoxymethyl, 2-methoxyethyl, 4-

ethoxybutyl, n-propoxyethyl and t-butylethyl. The term alkenyl, as usedherein, refers to an ethylenically unsaturated hydrocarbon group,branched or straight chain, having a chain length of two to twelvecarbon atoms, e.g. allyl, vinyl, 3-butenyl, Z-butenyl, Z-hexenyl andipropenyl. Whenever any of the foregoing terms are modified by the wordlower, the chain length of the group is not more than six carbon atomswith the exception of lower alkoxyalkyl in which event a total chainlength of twelve carbon atoms is the maximum.

The following examples are provided to illustrate the present invention.Temperature is given in degrees centigrade.

EXAMPLE 1 To a solution of 25.4 g. of 3,7,11-trimethyldodeca-2,4-IO-trienoyl chloride in ether is added 12.4 g. of ethylmercaptan and11.8 g. of pyridine at -40. The mixture is allowed to stand at 0 forabout 3 hours and then is diluted with ether and water and separated.The ether phase is washed with dilute aqueous sodium hydroxide, dilutehydrochloric acid and then water, dried and solvent removed to yieldethyl 3,7,11-trimethyl-thioldodeca-2,4, IO-trienoate.

The process of this example is repeated using each of the acid chloridesunder column VII to prepare the respective thiol ester under columnVIII.

(VII) ,7,1 1-trimethyltrideca-2,4,lo -trienoyl chloride 3 3,1l-dimethyl-7-ethyltrideca-2,4,10-trienoyl chloride7,11-diethyl-3-methyltrideca-2,4,10-trien0yl chloride I3,8,12-trimethyltrideca-2,4,1l-trienoyl chloride 3,7,l0-trimethylundeca2,4,9-trienoyl chloride 3,7,l0-trimethyldodeca-2,4,9-trienoyl chloride3,6,l0-trimethylundeca-2,4,9-trienoyl chloride 7,11-dimethyldodeca-2,4,10-trienoyl chloride 7 1 1-dimethyltrideca-2,4,IO-trienoyl chloride 7-ethyl-1l-methyltrideca-2,4,10-trienoyl chloride7,1 1-diethyltrideca-2,4, 10-trienoyl chloride8,12-di'methyltrideca-2,4,1 l-trienoyl chloride7,10-dimethylundeca-2,4,9-trienoyl chloride7,10-dimethyldodeca-2,4,9-trienoyl chloride6,10-dimethylundeca-2,4,9-trienoyl chloride (VIII) Methylmercaptan isreacted with each of the trienoylchlorides above using the procedure ofthis example except that the reaction mixture is prepared at about 10and the reaction is carried out in a sealed vessel to prepare therespective methyl thiol esters, e.g. -methyl3,7,11-trimethylthioldodeca-2,4,IO-trienoate, methyl3,7,11-trimethy1-thioltrideca-2,4,10-trienoate, methyl 3,11dimethyl-7-ethylthioltrideca-2,4,10-trienoate, etc.

6 EXAMPLE 2 3,7,1l-trimethyltrideca-2,4,IO-trienoyl chloride (18 g.) isadded slowly to ethyl lead mercaptide (13.4 g.) covered with ether. Themixture is allowed to stand overnight and then is filtered. The filtrateis evaporated under reduced pressure to yield ethyl3,7,11-trimethyl-thioltrideca-2,4,10-trienoate which can be purified bychromatography.

EXAMPLE 3 To a mixture of 24 g. of ethyl3,7,11-trimethyl-thioldodeca-2,4,10-trienoate in 75 ml. of ether, cooledin an ice-bath, is slowly added 0.1 mole of perphthalic acid in ether.Then the reaction mixture is allowed to stand for about 30 minutes. Themixture, at room temperature, is shaken with dilute aqueous sodiumhydroxide and then separated. The organic phase is washed with water,dried over magnesium sulfate and evaporated under reduced pressure toyield ethyl 10,11-oxido-3,7,1l-trimethyl-thioldodeca-2,4-dienoate, whichis purified by chromatography on neutral silica gel.

The above process is repeated using each of the unsaturated esters undercolumn VIII to prepare the respective epoxide under column IX.

ethyl 10,11-oxido-3,7,1 1-trimethyl-thioltrideca-2,4-

dienoate ethyl 10,1 1-oxido-3,1 1-dimethyl-7-ethy1-thioltrideca-2,4-

dienoate ethyl 10,1 1-oxido-7,11-diethyl-3-methyl-thioltrideca-2,4-

dienoate ethyl 11,12-0xido-3,8,1Z-trimethyl-thioltrideca-2,4-

dienoate ethyl 9,10-oxido-3,7,10-trimethyl-thioltrideca-Z,4-

dienoate ethyl 9,l0-oxido-3,7,l0-trimethyl-thioldodeca-2,4-

dienoate ethyl 9,10-oxido-3,6,l0-trimethyl-thiolundeca-2,4,-

dienoate ethyl 10.1 1-oxido-7,1 1-dimethyl-thioldodeca-2,4-

dienoate ethyl 10,1 1-oxido-7,1l-dimethyl-thioltrideca-2,4-

dienoate ethyl 10,1 l-oxido-l 1-methyl-7-ethyl-thioltrideca-2,4-

dienoate ethyl 10,1 1-oxido-7,1 1-diethyl-thioltrideca-2,4-dienoatedienoate ethyl 1 1,12-oxido-8,1Z-dimethyl-thioltrideca-2,4-

dienoate ethyl 9,10-oxide-7,10-dimethyl-thiolundeca-Z,4-dienoate ethyl9,10-oxido-7,10-dimethyl-thioldodeca-2,4-dienoate ethyl 9,10-oxido6,10-dimethyl-thiolundeca-2,4-dienoate EXAMPLE 4 Part A: Into a mixtureof 2 g. of ethyl 10,11-oxido-3,7,- 1l-trimethyldodeca-2,4-dienoate inml. of ether, there is slowly introduced one equivalent of hydrogenchloride at 0. The mixture is allowed to stand for about 12 hours. Thenthe mixture is washed with 5% aqueous sodium bicarbonate solution, driedover sodium sulfate and evaporated to yield a mixture of ethylll-chloro-lO-hydroxy- 3,7,11-trimethyldodeca-2,4-dienoate and ethylll-hydroxy 10 chloro 3,7,11 trimethyldodeca-2,4-dienoate which areseparated by chromatography.

By using hydrogen bromide in place of hydrogen chloride, there isprepared ethyl 11-bromo-10-hydroxy-3,7,11- trimethyldodeca-2,4-dienoateand ethyl 11-hydroxy-10- bromo-3,7,l1-trimethyldodeca-2,4-dienoate.

Part B: To a stirred solution of 1 g. of ethyl ll-chloro-10-hydroxy-3,7,11-trimethyldodeca-2,4-dienoate in 10 ml. of acetone,cooled to 0, is added under nitrogen, a solution of 8 N chromic acid(prepared by mixing chromium trioxide, cone. sulfuric acid and water)until the color of the reagent persists in the mixture. The mixture isthen stirred for one minute at 5 and diluted with water. The product isextracted with ether, washed with water and dried to yield ethyl11-chloro-10-oxo-3,7,1l-trimethyldodeca-2,4-dienoate.

Part C: To 1 g. of ethylll-chloro-10-oxo-3,7,1l-trimethyldodeca-2,4-dienoate in 2.0 ml. ofdimethylformamide is added 26 mg. of sodium azide and the temperaturebrought to 85 After about 3.5 hours, the reaction is cooled to roomtemperature. The reaction is diluted with pentane and water, separatedand the aqueous phase extracted with pentane/ ether. The combinedorganic phases are washed with saturated sodium chloride solution, driedover magnesium sulfate and solvent evaporated to yield ethyl11-azido-10-oxo-3,7,1l-trimethyldodeca-2,4-dienoate.

Part D: To 0.9 g. of the above prepared azido ketone in 2.0 ml. ofanhydrous methanol is added about 4 mg. of sodium borohydride. Afterabout one hour, water and ether is added and the layers separated. Theaqueous layer is extracted with ether and combined with the organiclayer which is washed to neutrality using saturated sodium chloride. Theorganic phase is then dried over magnesium sulfate and solvent removedto yield ethyl 11 azido 10 hydroxy 3,7,11 trimethyldodeca 2,4- dienoate.Using silica gel, the diastereomeric azide alcohols can be resolved, ifdesired.

Part E: A solution of 80 mg. of crude ethylll-azidol0-hydroxy-3,7,11-trimethyldodeca-2,4-dienoate and 10 ml. of a0.3 M triethylamine in pentane is cooled to -5. Then 200 mg. of mesylchloride is added. After 45 minutes, the reaction is poured onto ice andether is added. The organic phase is washed with dilute HCl, saturatedsodium bicarbonate, saturated sodium chloride and then dried over sodiumsulfate and solvent removed to yield the corresponding l0-mesylate.

Part F: Anhydrous CoBr (146 mg.) is dissolved in ml. of absolute ethanoland then 312 mg. of dipyridyl is added followed by 76 mg. of sodiumborohydride at 0 under argon.

To 35 mg. of the above prepared IO-mesylate in 0.8 ml. of ethanol at 0,under argon, is added 0.20 ml. of the above prepared reducing solutionand after several minutes an additional 0.5 ml. of the reducing solutionis added. After 0.5 hour, the reaction is poured into water and etheradded. The organic phase is washed with saturated sodium chloridesolution, dried over magnesium sulfate and solvent removed to yieldethyl 10,11-imino-3,7, 11-trimethyldodeca-2,4-dienoate which can bepurified by chromatography.

EXAMPLE 5 To a mixture of 2 g. of methyl3,7,11-trimethyl-thioltrideca-2,4,l0-trienoate in 150 ml. of methylenechloride at 0 is slowly added 1.0 molar equivalent of m-chloroperbenzoicacid in 100 ml. of methylene chloride. The resulting mixture is allowedto stand for 30 minutes at 0 and then washed with 2% aqueous sodiumsulfite solution, with 5% aqueous sodium bicarbonate solution and withwater, dried over sodium sulfate and evaporated to yield methyl10,11-oxide-3,7,ll-trimethyl-thioldodeca- 2,4-dienoate which is purifiedby chromatography.

EXAMPLE 6 The process of Example 4(A) is repeated using the epoxides ofExample 3 to prepare the respective halohydrins, e.g., ethyl11-chloro-10-hydroxy-3,7,1l-trimethylthioldodeca-2,4dienoate, ethyl1l-hydroxy-10-chloro-3,7,- 1l-trimethyl-thioldodeca-2,4-dienoate, ethyl11-chloro-10- 8 hydroxy-3,7,1l-trimethyl-thioltrideca-2,4 dienoate,ethyl 11 hydroxy 10 chloro 3,7,11 trimethyl thioltrideca-2,4-dienoate,etc.

EXAMPLE 7 Following the procedure of Example 4(B), ethyl 11- chloro 10oxo 3,7,11 trimethyl thioldodeca 2,4- dienoate is prepared from ethyl11-chloro-10-hydroxy- 3,7,1 1 trimethyl thioldodeca 2,4 dienoate. Ethyl11- chloro-l 0-oxo-3,7, 1 1-trimethylthioldodeca-2,4-dienoate is used asthe starting material in the reaction sequence of Example 4, parts C, D,E and F to prepare ethyl 10,1l imino-3,7,l1 trimethyl thioldodeca2,4-dienoate. In the same way, other ll-chloro-lO-hydroxy orll-bromo-lO- hydroxy compounds of Formula A such as those of Example 6are converted into the respective aziridine (Z taken with Z is imino) asthe final product.

What is claimed is:

1. A compound selected from those of the following formula:

m is zero or the positive integer one, two or three;

n is the positive integer one, two or three;

Z is bromo, chloro, fluoro or hydroxy;

Z is bromo, chloro, fluoro or hydroxy; and

R is lower alkyl, provided that when Z is bromo, chloro or fluoro-then Zis hydroxy and when Z is hydroxythen Z is bromo, chloro or fiuoro, R ishydrogen or lower alkyl and R R and R are respectively lower alkyl.

2. A compound according to claim 1 wherein R is hydrogen or methyl andeach of R R and R is methyl or ethyl.

3. A compound according to claim 2 wherein m is one and n is one or two.

4. A compound according to claim 3 wherein n is two; Z is hydroxy; Z ischloro; and R is methyl.

5. A compound according to claim 3 wherein n is two; Z is chloro; Z ishydroxy; and R is methyl.

6. A compound according to claim 4 wherein R is methyl.

7. A compound according to claim 5 wherein R is methyl.

8. A compound according to claim 6 wherein R is ethyl.

9. A compound according to claim 7 wherein R is ethyl.

10. The compound, ethylll-chloro-l0-hydroxy-3,7,1ltrimethyl-thioldodeca-2,4-dieuoate, accordingto claim 8.

References Cited FOREIGN PATENTS 2/1966 Republic of South Africa260-3268, 326.5 R, 327 E, 268 R, 247 R, 247.7 A, 293.9, 2935 D; 424301 4UNITED STATES PATENT OFFICE CERTIFICATE 6F CQRRECTION Patent ,322 DatedDecember 25 1973 ln en fl Clive A. Henrick and John B. Siddall It iscertified that error appears in the above-identified patent and thatsaid Letters Patent are hereby corrected as shown below:

Page 1, lines 3, 4 and 5 change "Clive A. Henrick, 1621 Channing Ave.94304, and John B. Siddall, 2470 Greer St. 94303, both of Palo Alto,Calif."

to read:

-C1ive.A. Henrick and John B. Siddall, both of- Palo Alto,

Calif. assignors to Zoecon Corp. Palo Alto, Calif. a corporation ofDelaware.

Signed and sealed this 9th day of April 197M.

(SEAL) Attes'b:

EDWARD M.FL,ETCHER,JR. C. MARSHALL DANN Attesting Officer Commissionerof Patents FO PO-1O5OHO-G9) USCOMM-DC seam-ps9 I a U S, GOVERN MFN'IPRINTING OFFICE 1 '969 0*366-334 7

